The Journal of Experimental Medicine
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Published online 17 September 2001. doi:10.1084/jem.194.6.707
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© The Rockefeller University Press, 0022-1007/2001/9/707/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 6, September 17, 2001 707-718

Original Article

Phenotypic and Functional Analysis of Cd8+ T Cells Undergoing Peripheral Deletion in Response to Cross-Presentation of Self-Antigen

Javier Hernandeza, Sandra Aunga, William L. Redmonda, and Linda A. Shermana

a Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
The Scripps Research Institute, Dept. of Immunology IMM-15, 10550 North Torrey Pines Road, La Jolla, CA 92037.858-784-8298858-784-8052

lsherman{at}scripps.edu

Not all T cells specific for autoantigens are eliminated in the thymus, and therefore alternate mechanisms are required to prevent potentially autoreactive T cells from developing into effectors. Adoptive transfer of CD8+ T cells from influenza hemagglutinin-specific Clone 4 TCR transgenic mice into mice that express hemagluttinin in the pancreatic islets results in tolerance. This is preceded by activation of Clone 4 T cells that encounter antigen cross-presented in the draining lymph nodes of the pancreas. In this report we compare the phenotype, function, and costimulatory requirements of Clone 4 T cells activated by endogenous self-antigen, with Clone 4 T cells stimulated by influenza virus. The cells undergoing tolerance upregulate both CD69 and CD44, yet only partially downregulate CD62L, and do not express CD49d or CD25. Most importantly, they lack the ability to produce interferon-{gamma} in response to antigen and show no cytolytic activity. Clone 4 T cells disappear after several cycles of division, apparently without leaving the site of initial activation. Surprisingly, despite the fact that such stimulation occurs through recognition of antigen that is cross-presented by a professional antigen-presenting cell, we find this activation is not dependent on costimulation through CD28. These data demonstrate that the recognition by naive CD8+ T cells of cross-presented self-antigen results in localized proliferation and deletion, without the production of effector cells.

Key Words: cytotoxic T lymphocytes • peripheral tolerance • T cell activation • B7 • IFN-{gamma}

Abbreviations used in this paper: CFSE, 5- and 6-carboxy-fluorescein succinimidyl ester; HA, hemagglutinin.

© 2001 The Rockefeller University Press


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